In 2013 an estimated 238,590 men will be diagnosed with carcinoma of the prostate (CaP) and an estimated 29,720 men will die from the disease [1]. This malignancy is the second leading cause of cancer-related death in men in the United States. In addition, African American (AA) men have the highest incidence and mortality from CaP compared with other races [1]. The racial disparity exists from presentation and diagnosis through treatment, survival, and quality of life [2]. Researchers have suggested that socio-economic status (SES) contributes significantly to these disparities including CaP-specific mortality [3]. As well, there is evidence that reduced access to care is associated with poor CaP outcomes, which is more prevalent among AA men than Caucasian American (CA) men [4].
However, there are populations in which AA men have similar outcomes to CA men. Sridhar and colleagues [5] published a meta-analysis in which they concluded that when SES is accounted for, there are no differences in the overall and CaP-specific survival between AA and CA men. Similarly, the military and veteran populations (systems of equal access and screening) do not observe differences in survival across race [6], and differences in pathologic stage at diagnosis narrowed by the early 2000s in a veterans' cohort [7]. Of note, both of these studies showed that AA men were more likely to have higher Gleason scores and PSA levels than CA men [6, 7].
While socio-economic factors may contribute to CaP outcomes, they do not seem to account for all variables associated with the diagnosis and disease risk. Several studies support that AA men have a higher incidence of CaP compared to CA men [1, 8, 9]. Studies also show that AA men have a significantly higher PSA at diagnosis, higher grade disease on biopsy, greater tumor volume for each stage, and a shorter PSA doubling time before radical prostatectomy [10-12]. Biological differences between prostate cancers from CA and AA men have been noted in the tumor microenvironment with regard to stress and inflammatory responses [13]. Although controversy remains over the role of biological differences, observed differences in incidence and disease aggressiveness at presentation indicate a potential role for different pathways of prostate carcinogenesis between AA and CA men.
Over the past decade, much research has focused on alterations of cancer genes and their effects in CaP [14-16]. Variations in prevalence across ethnicity and race have been noted in the TMPRSS2/ERG gene fusion that is overexpressed in CaP and is the most common known oncogene in CaP [17, 18]. Accumulating data suggest that there are differences of ERG oncogenic alterations across ethnicities [17, 19-21]. Significantly greater ERG expression in CA men compared to AA men was noted in initial papers describing ERG overexpression and ERG splice variants [17, 21]. The difference is even more pronounced between CA and AA (50% versus 16%) in patients with high Gleason grade (8-10) tumors. [Ferrell et al., manuscript]. Thus, ERG is a major somatic gene alteration between these ethnic groups. Yet beyond TMPRSS2/ERG, little is known regarding the genetic basis for the CaP disparity between AA and CA men remains unknown [24].
Therefore, new biomarkers and therapeutic markers that are specific for distinct ethnic populations and provide more accurate diagnostic and/or prognostic potential are needed.